Studies On The Isocyanide-Based Multicomponent Reactions And The Synthesis,Biological Activities Of 3-azolylquinolines

Over the past decades,the utility of isocyanides has emerged as a powerful tool in organic,medicinal,and polymeric chemistry.Multicomponent reactions(MCRs)have attracted great attention in the synthesis of heterocyclic compounds,medicinal chemistry and natural product preparation due to their advantages of easily accessible starting materials,mild conditions,high atomic economy and good substrate tolerance.Meanwhile,the carbene-like reactivity of the isocyanide groups had been extensively exploited in the development of metal-catalyzed insertion reactions to construct various structural skeletons.In this dissertation,a series of novel heterocyclic compounds were synthesized by the combination of MCRs with Wittig reaction,aza-Wittig reaction and isocyanide insertion reaction.In addition,a series of 3-azolyl substituted quinoline derivatives were also synthesized by a sequential condensation/aza-Wittig reaction.The biological activities of all the obtained compounds above were investigated.1.The latest development and applications of Passerini reaction,Ugi reaction,Wittig reaction,aza-Wittig reaction,triazole and imidazole fungicides are reviewed.2.A facile synthesis of 4-tetrazolyl-substituted 4H-3,1-benzoxazines through sequential Passerini-azide/acylation/catalytic aza-Wittig reaction starting from 2-azidobenzaldehydes,trimethyl-silyl azide and isocyanides had been developed.The structure was confirmed by NMR spectra and mass spectrometry followed by evaluation of the bactericidal,insecticidal and fungicidal activities.3.New efficient synthesis of 1,2,4-trisubstituted furans ?-5 by a sequential Passerini/Wittig/isomerization reaction starting from Baylis-Hillman ?-bromo aldehydes ?-1 had been reported.Note that unexpected furan-2(3H)-one ?-6 was also obtained.Subsequently,the reaction rules were summarized and the structure was confirmed by X-ray crystal analysis,NMR spectra and mass spectrometry followed by evaluation of the bactericidal,insecticidal and fungicidal activities.4.The multifunctional odorless isocyano(triphenylphosphorany-lidene)acetate ?-3 was prepared as a new stable phosphorus ylide containing isocyanide group.A new one-pot four component synthesis of multisubstituted oxazoles ?-7 and fused oxazoles ?-13 by a cascade Ugi/Wittig(/aza-Wittig)process without Mumm rearrangement had been developed starting from the isocyano(triphenylphosphora-nylidene)acetates,aldehydes,amines and acids.Two component reactions of isocyano(triphenylphosphoranyl-idene)-acetates and acids also generated disubstituted oxazoles ?-8 in good yields.The structure was confirmed by NMR spectra and mass spectrometry followed by evaluation of the bactericidal,insecticidal and fungicidal activities.5.An efficient one-pot synthesis of quinazolin-4(3H)-ones ?-4 and benzoimidazo[2,1-b]Quinazolin-12(6H)-ones ?-5 via a domino Pd-catalyzed cross-coupling/carbodiimide-mediated cyclization process had been developed.It's worth mentioning that the benzoimidazo[2,1-b]quinazolin-12(6H)-ones ?-5 were directly obtained by twice Pd-catalyzed domino cyclization.The structure was confirmed by NMR spectra and mass spectrometry followed by evaluation of the bactericidal,insecticidal and fungicidal activities.6.A robust ligand-free palladium-catalyzed cascade reaction for the synthesis of diversely substituted isoindoline skeletons ?-5 through aerobic isocyanide insertion into Ugi-3CR accompanied by unexpected rearrangement has been developed starting from a series of aldehydes,amines,and isocyanides.The structure was confirmed by NMR spectra and mass spectrometry followed by evaluation of the bactericidal,insecticidal and fungicidal activities.7.A series of 3-azolyl substituted quinoline derivatives ?-4 had been obtained via a tandem condensation/aza-Wittig reaction starting from a mixture of 2-azidobenzaldehydes and ?-azolyl substituted esters.The structure was confirmed by NMR spectra and mass spectrometry followed by evaluation of the bactericidal,insecticidal and fungicidal activities,which revealed that some compounds exhibited better activity to those of commercialized pesticide such as triadimefon.